Francisco Castro e Sousa

Mitochondrial bioenergetics and posthepatectomy liver dysfunction

Liver regeneration requires an enormous energy supply. Experimental evidence suggests that mitochondrial function is of paramount importance for liver regeneration. However, this has not been investigated in the clinical setting. We aimed to: (i) evaluate changes in mitochondrial function during hepatectomy, especially after hepatic pedicle clamping; and (ii) correlate these changes with postoperative hepatocellular function and clinical outcome.

Prevalence and characteristics of Epstein–Barr virus-associated gastric carcinomas in Portugal

BackgroundGastric cancer (GC) is one of the most common malignant tumors of the digestive tract and is the third leading cause of cancer death worldwide. Epstein–Barr virus (EBV) has been associated with approximately 10% of the total cases of gastric carcinomas. No previous study has analyzed the prevalence of EBV infection in gastric cancer of the Portuguese population.MethodsIn the present study, we have analyzed 82 gastric carcinoma cases and 33 healthy individuals (control group) from Coimbra region for the presence of EBV by polymerase chain reaction (PCR) and by in situ hybridization (ISH) for EBV-encoded small RNAs (EBERs). The status of H. pylori infection was assessed by serology and by PCR.ResultsEBV was detected by PCR in 90.2% of stomach cancer cases, whereas EBERs were detected in 11%. In our series, EBV-associated gastric carcinoma (EBVaGC) were significantly associated with gender and the majority of them presented lymph node metastasis. These cases were generally graded in more advanced pTNM stages and, non-surprisingly, showed worse survival. H. pylori infection was detected in 62.2% of the gastric cancers and 64.7% of these patients were CagA+. On the other hand, the H. pylori prevalence was higher in the EBV-negative gastric carcinomas (64.4%) than in those carcinoma cases with EBV+ (44.4%).ConclusionsThe present study shows that prevalence of EBVaGC among Portuguese population is in accordance with the worldwide prevalence. EBV infection seems to be associated to poorer prognostic and no relation to H. pylori infection has been found. Conversely, the presence of H. pylori seems to have a favourable impact on patient’s survival. Our results emphasize that geographic variation can contribute with new epidemiological data on the association of EBV with gastric cancer.

Glucagon secretion after metabolic surgery in diabetic rodents

Excessive or inadequate glucagon secretion promoting hepatic gluconeogenesis and glycogenolysis is believed to contribute to hyperglycemia in patients with type 2 diabetes. Currently, metabolic surgery is an accepted treatment for obese patients with type 2 diabetes and has been shown to improve glycemic control in Goto-Kakizaki (GK) rats, a lean animal model for type 2 diabetes. However, the effects of surgery on glucagon secretion are not yet well established. In this study, we randomly assigned forty 12- to 14-week-old GK rats to four groups: control group (GKC), sham surgery (GKSS), sleeve gastrectomy (GKSG), and gastric bypass (GKGB). Ten age-matched Wistar rats served as a non-diabetic control group (WIC). Glycemic control was assessed before and 4 weeks after surgery. Fasting- and mixed-meal-induced plasma levels of insulin and glucagon were measured. Overall glycemic control improved in GKSG and GKGB rats. Fasting insulin levels in WIC rats were similar to those for GKC or GKSS rats. Fasting glucagon levels were highest in GKGB rats. Whereas WIC, GKC, and GKSS rats showed similar glucagon levels, without any significant meal-induced variation, a significant rise occurred in GKSG and GKGB rats, 30 min after a mixed meal, which was maintained at 60 min. Both GKSG and GKGB rats showed an elevated glucagon:insulin ratio at 60 min in comparison with all other groups. Surprisingly, the augmented post-procedural glucagon secretion was accompanied by an improved overall glucose metabolism in GKSG and GKGB rats. Understanding the role of glucagon in the pathophysiology of type 2 diabetes requires further research.

Mitochondria in Liver Regeneration: Energy Metabolism and Posthepatectomy Liver Dysfunction

Liver resection is the only curative therapy for most patients with hepatobiliary malignancies. Resection of a substantial amount of liver mass is only possible due to the liver’s remarkable capacity to regenerate. However, when this process is hampered Posthepatectomy Liver Failure (PHLF) ensues, resulting in increased postoperative mortality and morbidity. Being a highly energy dependent chain of events, liver regeneration is influenced by the energy status of the main parenchymal cell—the hepatocyte. Mitochondria are the powerhouses of eukaryote cells and key players in cell death. As such, they play a major role in the organ’s response to major resection. Although this subject has been the focus of investigation in the past, recent findings have led to a renewal of interest on disordered bioenergetics in liver surgery. In this Chapter we will scrutinize the experimental and clinical evidence supporting a major role for mitochondria in the liver’s response to resection, as well as the relevance of mitochondrial derangement in the pathophysiology of PHLF. Furthermore, as a significant proportion of patients undergoing hepatectomy have chronic liver diseases, namely cirrhosis, biliary obstruction, steatosis or sinusoidal obstruction syndrome, which are at increased risk of PHLF, we will recapitulate the disordered bioenergetics in the pathophysiology of these conditions. Finally, we will elaborate on the evidence for a definitive role of boosting energetic status of the liver parenchyma in improving the clinical results of hepatectomy.

Spontaneous Regression of Colorectal Liver Metastases

Spontaneous regression of cancer is a rare phenomenon, often of obscure etiology. We present the case of a 51-year-old female patient, whose colorectal liver metastases, diagnosed by CT scan and confirmed by MRI and per-operative US scan, underwent spontaneous necrosis, as demonstrated by pathological examination. She was submitted to left colectomy, splenectomy and total hysterectomy six years earlier followed by adjuvant chemotherapy, as treatment of the primary tumour (adenocarcinoma of the splenic angle of the colon, staged as pT3,N1,M0). She underwent a right hepatectomy to treat liver metastases, located in the segments VIII and V/VI of the liver; to date, she remains asymptomatic and disease-free. We hope this case may contribute to the characterization of a subset of patients whose malignancy spontaneously regresses, which may prove decisive in the development of new strategies for cancer treatment.